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KDM5A – Congenital Heart Disease

In a cohort of 30 families with congenital heart disease, whole-exome sequencing identified a likely deleterious KDM5A variant segregating with disease in one family (n=1 proband) (PMID:29555671). Although the exact nucleotide change was not specified, this observation provides preliminary genetic evidence. Functional characterization of RBP2 (KDM5A) revealed that pRB–RBP2 binding modulates chromatin-based transcriptional repression and promotes cellular differentiation in vitro (PMID:15949438), suggesting that KDM5A haploinsufficiency could perturb cardiac morphogenesis. No additional replication cohorts or heart-specific animal models have been reported to date. Key take-home: KDM5A is a candidate congenital heart disease gene that warrants further genetic and functional validation.

References

  • Circulation. Genomic and precision medicine • 2018 • A Screening Approach to Identify Clinically Actionable Variants Causing Congenital Heart Disease in Exome Data. PMID:29555671
  • Molecular cell • 2005 • Binding of pRB to the PHD protein RBP2 promotes cellular differentiation. PMID:15949438

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Single proband in one family with segregating KDM5A variant (n=1) [PMID:29555671]

Genetic Evidence

Limited

One family with a KDM5A variant segregating with CHD (PMID:29555671)

Functional Evidence

Limited

In vitro pRB–RBP2 binding and differentiation assays implicate KDM5A in developmental gene regulation (PMID:15949438)